Stanford Medicine scientists reported in Science Translational Medicine that Epstein–Barr virus (EBV) reprogrammed human immune cells and drove systemic lupus erythematosus. Using a single-cell sequencing method, the team found that about 25 of every 10,000 B lymphocytes from patients with lupus carried latent EBV, compared with fewer than one per 10,000 in healthy volunteers. In adults who are otherwise healthy, the virus usually resides in fewer than one-tenth of one percent of B cells, yet the proportion rose to roughly one in 400 among the patients.
“We think it applies to 100% of lupus cases,” said William Robinson, professor of immunology and rheumatology at Stanford University, according to the Guardian.
The group showed that a viral protein, EBNA2, switched on previously silent genes such as ZEB2 and TBX21, turning infected memory B cells into potent antigen-presenting cells that recruited helper and cytotoxic T cells and sustained body-wide inflammation.
The investigators isolated individual B cells from 11 people with lupus and 10 controls. Most infected cells were memory B cells whose antibodies reacted to nuclear material, a classic sign of the disease. “This study resolves a decades-old mystery,” said Shady Younis, an immunologist at Stanford and first author of the paper, the Guardian reported.
Lupus affects at least five million worldwide. About 90 percent of patients are women, a disparity often tied to oestrogen-driven B-cell activity. Symptoms range from joint pain and fatigue to rashes, and the illness can damage vital organs. Around five percent of cases are fatal, and available therapies only slow progression.
“It’s EBV infection in the context of the genetic and environmental milieu that predisposes one to lupus that together results in them getting lupus,” Robinson said, according to New Scientist.
Previous epidemiological work linked the virus to multiple sclerosis; people with lupus likewise carry high levels of antibodies against EBV proteins, and viral reactivation often coincides with disease flare-ups. Because about 94 percent of the global population acquires EBV, scientists said prevention will likely rely on vaccination, and several candidate vaccines are in early-stage trials. “Perhaps the strongest rationale yet for pursuing EBV vaccines to prevent lupus,” said Akiko Iwasaki, an immunologist at Yale University, in Scientific American.
Robinson argued that any effective shot would need to be administered early in life, before latent infection is established.
Therapies directed at infected B cells are also under study. Early trials of CAR T-cell therapy that depletes B cells have produced drug-free remission in some severe cases. “These CAR T-cell treatments seem to result in what we call long-term durable remission… and we think it’s possible that they might achieve this by getting rid of the EBV-infected B-cells,” Robinson told New Scientist. George Tsokos, a rheumatologist at Harvard Medical School, cautioned that B cells can persist in bone marrow and that it remains unproven that all infected cells are removed.
Researchers noted that EBV may use a similar mechanism to spark other autoimmune illnesses such as rheumatoid arthritis or Crohn’s disease. Robinson suggested that only certain viral strains might convert B cells into hyperactive antigen-presenting cells, a question that could influence future vaccine design and risk prediction.
The preparation of this article relied on a news-analysis system.